Human A-to-I RNA editing SNP loci are enriched in GWAS signals for autoimmune diseases and under balancing selection

Zhang, Hui; Fu, Qiang; Shi, Xuliang; Pan, Ziqing; Yang, Wenbing; Huang, Zichao; Tang, Tian; He, Xionglei; Zhang, Rui

doi:10.1186/s13059-020-02205-x

Cited by 11 publications

(10 citation statements)

References 57 publications

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“…SPAG6-ES might have a different function from SPAG6-FL. Here we found that SPAG6-ES inhibited the proliferation of porcine Sertoli cells and increased the apoptosis of cells, which is consistent with the results in Spag6-deficient mouse embryonic fibroblasts and SPAG6 silencing of SKM-1 cells (Zhang, Fu, et al, 2020;Zhang, Luo, et al, 2020;Zhang, Zhu, et al, 2020). SPAG6 promotes cell proliferation and inhibits apoptosis in Burkitt lymphoma cells (Zhang, Fu, et al, 2020;Zhang, Luo, et al, 2020;Zhang, Zhu, et al, 2020), which is in accordance with SPAG6-FL functions in porcine Sertoli cells.…”

Section: Discussionsupporting

confidence: 90%

SPAG6 c.900 T>C affects boar semen quality and blood–testis barrier function by creating a new splice acceptor site

et al. 2023

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Sperm associated antigen 6 (SPAG6) acts as a scaffolding protein in the center of the flagellar axoneme and has an impact on the maturation of the motility of mammalian sperm flagella and the maintenance of sperm structure. In our previous research, SPAG6 c.900 T>C in exon 7 and exon 7 skipped transcript was identified by analyzing RNA-seq data of testicular tissues from 60 day (sexually immature) and 180 day (sexually mature) Large White boars. Herein, we found porcine SPAG6 c.900 T>C to be associated with semen quality traits in Duroc, Large White and Landrace pigs. SPAG6 c.900 C can generate a new splice acceptor site, inhibit the occurrence of SPAG6 exon 7 skipping to a certain extent, thereby promote the growth of Sertoli cells and maintain the normal blood-testis barrier function. This study provides new insights into the molecular regulation of spermatogenesis and a new genetic marker for the improvement of semen quality in pigs.

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Section: Discussionsupporting

confidence: 90%

SPAG6 c.900 T>C affects boar semen quality and blood–testis barrier function by creating a new splice acceptor site

et al. 2023

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“…RNA editing events have been reported to suffer under selection pressure. Zhang Rui’s team has found that RNA-edited SNP sites are highly enriched near autoimmune disease-related sites represented by Crohn’s disease, asthma, and allergic dermatitis and are subject to balanced selection ( 40 ). Duan’s group has reported that there are a large number of non-synonymous RNA editing sites (Nonsyn) that change amino acids in Drosophila , which show adaptive signals and are subject to positive natural selection ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide identification of A-to-I RNA editing events provides the functional implications in PDAC

Yue

Liang

et al. 2023

Front. Oncol.

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IntroductionRNA editing, a wide-acknowledged post-transcriptional mechanism, has been reported to be involved in the occurrence and development of cancer, especially the abnormal alteration of adenosine to inosine. However, fewer studies focus on pancreaticcancer. Therefore, we aimed to explore the possible linkages between altered RNA editing events and the development of PDAC.MethodWe characterized the global A-to-I RNA editing spectrum from RNA and matched whole-genome sequencing data of 41 primary PDAC and adjacent normal tissues. The following analyses were performed: different editing level and RNA expression analysis,pathway analysis, motif analysis, RNA secondary structure analysis, alternative splicing events analysis, and survival analysis.The RNA editing of single-cell RNA public sequencing data was also characterized.ResultA large number of adaptive RNA editing events with significant differences in editing levels were identified, which are mainly regulated by ADAR1. Moreover, RNA editing in tumors has a higher editing level and more abundant editing sites in general. 140genes were screened out since they were identified with significantly different RNA editing events and were significantly different in expression level between tumor and matched normal samples. Further analysis showed a preference that in the tumor-specific group, they are mainly enriched in cancer-related signal pathways, while in the normal tissue-specific group, they are mainly enriched in pancreatic secretion. At the same time, we also found positively selected differentially edited sites in a series of cancer immune genes, including EGF, IGF1R, and PIK3CD. RNA editing might participate in pathogenisis of PDAC through regulating the alternative splicing and RNA secondary structure of important genesto further regulate gene expression and protein synthesis, including RAB27B and CERS4. Furthermore, single cell sequencing results showed that type2 ductal cells contributed the most to RNA editing events in tumors.ConclusionRNA editing is an epigenetic mechanism involved in the occurrence and development of pancreatic cancer, which has the potential to diagnose of PDAC and is closely related to the prognosis.

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“…A recent study introduced the role of the IL6R-STAT3-ADAR1 axis in the oncogenicity of multiple myeloma (47). It should be noted that enrichment of ADAR SNP loci was identified in GWAS signals for autoimmune diseases (48). Corresponding to the evidence from the rna-seq dataset, rs12059682 C>T mutation could lead to a lower level of ADAR in the lymphocyte and fibroblast.…”

Section: Discussionmentioning

confidence: 99%

Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific

Hong

et al. 2021

Front. Immunol.

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ObjectivesTo find out the genetic association between IL6 and autoimmune arthritis.MethodsWe performed a two-sample Mendelian randomization (MR) study using multiple genome-wide association studies (GWAS) datasets. Furthermore, a sex-stratified MR study was performed to identify sexual dimorphism in the association between IL6 and autoimmune arthritis. Then, LocusZoom plots were displayed based on the IL6R gene region to present evidence of genetic colocalization between diseases.ResultsThe MR result denoted a genetic association between the increased level of IL-6 signaling and risk of RA (β=0.325, 95%CI 0.088, 0.561, p=7.08E-03) and AS (β=1.240, 95%CI 0.495, 1.980, p=1.1E-03). Accordingly, sIL6R was found to have negatively correlation with the onset of RA (β=-0.020, 95%CI -0.0320, -0.008, p=1.18E-03) and AS (β=-0.125, 95%CI -0.177, -0.073, p=2.29E-06). However, no genetic association between IL6/sIL6R and PsA was detected. The gender-stratified MR analysis showed that IL6 was associated with AS in the male population, with RA in the female population, and with PsA in the male population. Additionally, ADAR, a gene identified by a sensitive test, could be the reason for the nonsignificant association between IL6 and PsA in a pooled population.ConclusionOur findings showed that the overactive IL6 signal pathway led to autoimmune arthritis, especially in RA and AS. Sexual difference was also observed in IL6-intermediate susceptibility to autoimmune arthritis.

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Human A-to-I RNA editing SNP loci are enriched in GWAS signals for autoimmune diseases and under balancing selection

Cited by 11 publications

References 57 publications

SPAG6 c.900 T>C affects boar semen quality and blood–testis barrier function by creating a new splice acceptor site

SPAG6 c.900 T>C affects boar semen quality and blood–testis barrier function by creating a new splice acceptor site

Genome-wide identification of A-to-I RNA editing events provides the functional implications in PDAC

Genetic Associations Between IL-6 and the Development of Autoimmune Arthritis Are Gender-Specific

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